DESCRIPTION: (Applicant's Abstract) Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections occur with alarming frequency in persons who misuse alcohol and illicit drugs. In East Baltimore, 80 percent of HIV-infected injection drug users also have HCV infection and one-half acknowledges regular, heavy alcohol use. This disease cluster may cause cirrhosis since HIV infection and heavy alcohol use are the two conditions that accelerate progression of hepatitis C. Recently the significance of these cofactors has been magnified by improved anti-retroviral treatments that dramatically reduce other opportunistic infections but may themselves cause liver toxicity. Accordingly, the 1999 US Public Health Service guidelines for management of HIV opportunistic infections considered hepatitis C but withheld recommendations for medical management because of the paucity of supporting data. In this investigation, we hypothesize that treatment of HIV and HCV infections will reduce progression of liver disease, after controlling for alcohol use. To test the hypothesis, we will first examine the success of prior anti-retroviral use with respect to liver fibrosis and then the change in fibrosis over three years of anti-retroviral experience. In addition, we will examine the effect of alfa-interferon based treatment for HCV infection with respect to fibrosis changes and eradication of HCV. Innovative tools will be tested to assess liver fibrosis (morphometrics), predict liver fibrosis (markers), and measure use of alcohol and medical adherence (A-CASI). Given the experience of the investigative team and the extensive preliminary data, we anticipate providing data that will directly affect forthcoming guidelines for the medical management of HIV-HCV coinfected persons.